While adult smoking prevalence stagnates in the United States, new noncombustible tobacco products like electronic cigarettes (e-cigarettes) are gaining force. Indeed, recent reports from the tobacco industry (Altria, Lorillard, and Reynolds American) and e-cigarette manufacturers (NJOY) confirm an aggressive commitment to the sale of these products, and national estimates of e-cigarette prevalence reflect a shift in awareness and use. Data from the analytical laboratory suggest that e-cigarette nicotine liquids and associated aerosol contain variable amounts of nicotine and very low levels of carcinogens relative to tobacco cigarettes. Acute clinical studies of e-cigarettes indicate significant nicotin delivery under some conditions and no carbon monoxide (CO) exposure. It is unknown how e- cigarettes affect tobacco use behavior and toxicant exposure, particularly among those who continue to smoke cigarettes. This project adapts a previous model used to evaluate potential reduced exposure products ('PREPs') to examine how e-cigarettes affect measures of harm potential among cigarette smokers. Current dual users of cigarettes and e-cigarettes (N=28) will complete four, 5-day conditions that differ by tobacco products used ad libitum: 1) cigarette and e-cigarette (dual use), 2) cigarette-only, 3) e-cigarette-only, and 4) no tobacco/nicotine. Condition order will be assigned using a balanced Latin square design, and products will be participants' own brand cigarettes and e-cigarettes. Tobacco product consumption will be assessed using physical product counts and daily monitoring, and toxicant exposure will be measured thrice weekly via using CO, urinary cotinine, and the sum of two urinary metabolites of the tobacco-specific nitrosamine and potent lung carcinogen NNK (total NNAL). Data from the dual and single product use conditions will be used to assess changes in tobacco product consumption. Data from all conditions will be used to assess changes in toxicant exposure during dual use in comparison to single product use and no tobacco/nicotine use. Secondary analyses include evaluating cardiovascular and subjective effects associated with dual use of cigarettes and e-cigarettes and characterizing dual use patterns over a 5-day period. Results from this exploratory R21 project will address whether dual use of cigarettes and e-cigarettes decreases, has little effect on, or increases measures of harm potential relative to single product use and no tobacco/nicotine use. In light of the lack of previous literature in this area and increasing e-cigarette prevalence and product promotion, this research will be essential to inform Center for Tobacco Product deliberations on how best to regulate approval and marketing of existing and new e-cigarette products. This project will also aid the development of a future R01 grant submission related to a longer term and more detailed assessment of the effects of e-cigarette use on cigarette smoking behavior.